This research is a biological approach to selective programming and expansion of immunologically naive murine lymphoid cells by incubation with polyadenylic acid containing RNA extracted from specifically sensitized lymphoid cells. The objectives include: (1) to utilize xenogeneic or allogeneic lymphoid cell-RNA to convert cells to specific antibody production; and then selecting, expanding, and perpetuating these limited numbers of RNA-converted cells by cell fusion with NS-2 or SP2/O myeloma cells; (2) to screen by an enzyme-linked immunosorbent assay (ELISA) fused hybrid cells for the production of specific antibodies against RNA-donor immunogens, keyhole limpet hemocyanin (KLH), DNP-ovalbumin, or line-10-line-1 tumor antigens; (3) to clone by limiting dilution techniques, stable, antibody-producing RNA-derived hybrids; (4) to fuse lymphoid-cell mixtures from immunosuppressed mice receiving syngeneic cells treated with RNA in vitro and injected in vivo and showing evidence and persistence of specific antibody in the serum; (5) to assess whether surface idiotypes are present on converted hybrids by anti-idiotypic antibodies and/or antigen-binding rosette assays; (6) to isolate and characterize RNA-derived clonal antibodies and/or surface idiotypes and assess whether they are of murine and/or cavine origin; (7) to define the technical parameters necessary for successful reproducible RNA-derived cell fusion and to assess the lymphoid cell-surface marker characteristics and numbers of recipient lymphoid cells with these markers; and (8) to extract enriched, homogenous RNA species from RNA-derived cell clones for serial conversion-cell fusion experiments and further isolation and/or characterizations. Results indicate selective enrichment of RNA species mediating the conversion of murine lymphoid cells utilizing RNA species extracted from several RNA-derived hybridomas. RNA extracted from RNA-derived hybridomas producing substances reactive with KLH or DNP-ovalbumin can serially transfer these specific reactivities to new lymphoid cell populations for hybridoma fusion which results in greater numbers of positive colonies evident upon initial screening with the ELISA assay. Hybridomas can also be developed upon isolation of spleen cells from immunosuppressed mice receiving injections of RNA-treated spleen cells, and showing specific anti-KLH and anti-DNP-ovalbumin antibodies in their serum. Fluorescent activated cell sorting analysis of cell lines developed by RNA conversion indicate binding of: (1) anti-idiotypic specific protein-A separated fractions, and (2) FITC conjugated immunogens. (AG)